Functionalized nanocarrier-based intranasal drug delivery of rivastigmine tartrate for enhanced brain exposure: a pharmacokinetic and biodistribution evaluation

AIMS: To develop and evaluate a polyethylene glycol (PEG)-functionalized multi-walled carbon nanotube (MWCNT)-based intranasal delivery system for rivastigmine tartrate (RT) to improve systemic exposure and brain delivery for Alzheimer's disease (AD). MATERIALS AND METHODS: factorial design, and characterized for particle size, zeta potential, entrapment efficiency, morphology, in vitro release, ex vivo nasal permeation, pharmacokinetics, brain biodistribution, cytocompatibility, and neuroprotective activity. RESULTS: The optimized formulation showed an entrapment efficiency of 90.92%, particle size of 176.7 nm, and zeta potential of -24.1 mV. Sustained drug release and efficient permeation across goat nasal mucosa were observed. Intranasal administration increased plasma exposure, producing approximately 5-fold higher relative bioavailability and a 4.1-fold increase in brain exposure compared with oral administration. In SH-SY5Y cells, the formulation reduced rotenone-induced oxidative stress and improved cell viability, indicating neuroprotective potential. CONCLUSIONS: PEGylated MWCNT-mediated intranasal delivery enhanced rivastigmine bioavailability and brain exposure while demonstrating neuroprotective activity in vitro. These findings support further investigation of this nanocarrier platform as a strategy for brain-targeted delivery of rivastigmine.